BIOE 301/362

Geoff PreidisMD/PhD candidateBaylor College of Medicinepreidis@post.harvard.edu

Lecture Three:Leading Causes of Mortality, Ages

15-44

Review of Lecture Two:Leading Causes of Mortality, Birth-

Age 4 Developing world

1. Perinatal conditions2. Lower respiratory infections3. Diarrheal diseases4. Malaria

Developed world1. Perinatal conditions2. Congenital anomalies3. Lower respiratory infections4. Unintentional injuries

Group 1Group 1 Communicable diseases, maternal/perinatal conditions, nutritional deficienciesGroup 2Group 2 Non-communicable diseases (cardiovascular, cancer, mental disorders)Group 3Group 3 Injuries

Ratio of Mortality Rate

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0-4 5-14 15-29 30-44 45-59 60-69 70-79 80+

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WHO, 2002

1. Perinatal Conditions

Question: What is the #1 way to prevent septicemia in a newborn in the developing world?

1. Perinatal Conditions

http://www.path.org/projects/clean-delivery_kit.php

2. Lower Respiratory Infections

Question: How can a busy health worker (or a parent) quickly screen for pneumonia in a child?

2. Lower Respiratory Infections

3. Diarrheal Diseases

Question: What is the #1 way to prevent diarrheal illness in a newborn?

3. Diarrheal Diseases

4. Malaria

Question: How was malaria eradicated from the southern U.S.? What are the challenges with implementing this technology in less developed countries?

Challenges for implementing vector control technologies in developing countries Mapping areas that are difficult

to access Poor communication Direction – Transfer of vector

control efforts from malaria control authorities to local primary health care center

Financial support – decreased standard of living from wars, environmental factors, migration

Corruption, graft

4. Malaria

http://www.cdc.gov/malaria/history/

Leading Causes of Mortality Ages 15-44

Developing World1. HIV/AIDS2. Unintentional injuries3. Cardiovascular diseases4. Tuberculosis

Developed World1. Unintentional injuries2. Cardiovascular diseases3. Cancer4. Self-inflicted injuries

1. HIV/AIDS

Burden of HIV/AIDS Pathophysiology of HIV Clinical course of HIV/AIDS Highly Active Antiretroviral Therapy Prevention of Mother to Child

Transmission (PMTCT)

Burden of HIV/AIDS Worldwide

33.0 M people living with HIV/AIDS (2 M children)

25 M killed, 11.5 M orphans in Africa alone 2007:

2.0 M deaths 2.7 M new HIV infections 14% of new infections occurred in children (<15 yrs)

2/3 of those with AIDS and 3/4 of all AIDS deaths are in sub-Saharan Africa

7400 new infections per day 96% in low- and middle-income countries 1000 children Source: 2008 AIDS Epidemic Update, UNAIDS/WHO

http://www.who.int/whr/2004/en/charts_en.pdf

http://www.who.int/whr/2004/en/charts_en.pdf

http://www.who.int/whr/2004/en/charts_en.pdf

Burden of HIV/AIDS in the U.S.

1.2 M people have HIV/AIDS (prevalence) 56,000 new infections per year (incidence) Only 7 countries in the world have more

people living with HIV than the U.S. Routes of transmission:

Unsafe sex between men (53%) High-risk heterosexual intercourse (31%) Non-sterile drug injection equipment (12%)

Source: 2008 AIDS Epidemic Update, UNAIDS/WHO

Burden of HIV/AIDS in the U.S.

Racial and ethnic minorities are disproportionately affected: 50% of HIV diagnoses are African-Americans (15%

pop) The rate of new HIV diagnoses was 21x higher in

African-American women than in Caucasian women Women are increasingly affected:

The proportion of women among new HIV/AIDS diagnoses have risen from 15% to 26% in 10 years

Question: Why is the prevalence of HIV in the U.S. continuing to increase?

Source: 2008 AIDS Epidemic Update, UNAIDS/WHO

Pathophysiology of HIV/AIDS

Michael W. Davidson at Florida State University

http://bayloraids.org/curriculum/

Pathophysiology of HIV/AIDSIntegrase InhibitorsFusion Inhibitors

Pathophysiology of HIV/AIDS

http://bayloraids.org/curriculum/

Clinical Course of HIV/AIDS

Clinical Course of HIV/AIDS

http://hivinsite.ucsf.edu/topics/aids_basics

Clinical Course of HIV/AIDS

http://bayloraids.org/curriculum/

HIV/AIDS Therapy HIV can rapidly mutate to quickly

develop resistance to a single drug Resistance develops much more

slowly to drug combinations Goal of ART:

Reduce viral levels to undetectable levels

Has reduced death rate in US and Europe by 80%

HIV/AIDS Therapy

http://www.who.int/whr/2004/en/charts_en.pdf

http://www.who.int/whr/2004/en/charts_en.pdf

6 million people living with AIDS are in need of HAART. 90% are in just 34 developing countries

Prevention of Mother to Child Transmission (PMTCT)

3 routes of transmission: Parentally (during pregnancy) Perinatally (during delivery) Breast feeding (through milk)

4 Core interventions: HIV testing and counseling ARV prophylaxis (ZDV, NVP) Safer delivery practices Safer infant-feeding practices

Reduces transmission from 30-40% to 4-6%

2. Unintentional Injuries

Burden of Unintentional Injuries Accident Physics Slowed Driver Reaction Time Prevention of Road Accidents

2. Unintentional Injuries

Burden of Unintentional Injuries

More than 1.25 M people ages 15-44 die from unintentional injuries each year

1 M deaths in developing countries, 1/4 M in developed countries

40x this number are injured Major cause of disability Leading cause is road accidents:

500,000 deaths per year in this age group 90% of these deaths occur in developing

countries

Road Accidents in the U.S. Rates declining steadily A leading cause of potential years of life lost 2008:

37,000 Americans killed 2,500,000 Americans injured Fatal accident rates 3X higher for males than for

females Motorcycles: 40X higher death rate per mile

traveled 39% of fatalities related to alcohol use

Burden of Unintentional Injuries

Accident Physics

Newton’s 2nd Law: F = m a a = dv/dt a = initial velocity/time to come to rest

In a crash: Velocity slows to zero in a very short

time Generates large forces

How can we reduce these forces?1. Reduce initial velocity of impact2. Extend time that it takes passengers to

come to rest

Prevention of Road Accidents

1. Reduce initial velocity of impact Excessive speed contributes to:

30% of deaths in developed countries 50% of deaths in developing countries

1. Reduce Initial Velocity of Impact

When drivers anticipate a crash, they have time to brake and reduce initial velocity

Factors which slow driver reaction time: Alcohol use Mobile phone use Poor visibility Driver inexperience

1. Reduce Initial Velocity of Impact

Alcohol impaired drivers have 17X increased risk of being in fatal crash

Alcohol use increases risk more in younger drivers

1 in 5 Americans will be involved in an alcohol-related crash at some time in their lives

TX BAC limit: 0.08+ g/dl is illegal Approx 3 drinks in a

140 lb individual Significant driving

impairment at just 0.04 BAC!

1. Reduce Initial Velocity of Impact

Mobile phone use: At any given daylight moment in US:

10% of drivers are using a cell phone Increases driver reaction time by 0.5-1.5 seconds Risk of crash is 4X higher when using a mobile phone Same as driving with a BAC of 0.09 g/ dl

6 states and D.C. have banned use of hand held phones while driving (CA, CT, NJ, NY, OR, WA) Partial bans in AR, AZ, CO, DE, GA, IL, IN, KY, LA, ME,

MD, MA, MI, MN, NE, NH, NM, NC, OH, PA, RI, TN, TX, UT, VA, WV

TX: Banned for novices (1st 12 mos) and in school crossing zones

Prevention of Road Accidents

2. Extending Time to Come to Rest: Crumple zones

Allow passengers additional time to decelerate

Seat belts Keep occupants in the passenger

compartment Stretch during impact Reduce risk of death in crash by 40-60%

Air bags When combined with seat belts, reduce risk

of serious and fatal injuries by 40-65% Child restraints:

Reduce risk of infant death by 71% and toddler death by 54%

Prevention of Road Accidents

3. Legislation: Speed Seat belts, Car seats, Air Bags Alcohol use Motorcycle helmets

4. Engineering: Restraints Safety standards

5. Education: Seat belts, Car seats, Air Bags Alcohol use

3. Cardiovascular Diseases

768,000 people ages 15-44 die as a result of cardiovascular disease every year

Most common causes: Ischemic heart disease (286,000 deaths) Cerebrovascular disease (159,000

deaths) Will be covered in depth in Lecture 4

Tuberculosis

www.ohsu.edu/library/hom/exhibits/exhimages/200501tb/openair_pavilions.jpg

4. Tuberculosis

Burden of Tuberculosis TB Pathophysiology Diagnosis of Tuberculosis Directly Observed Therapy

Burden of Tuberculosis Bacterial infection of the lungs caused by

Mycobacterium tuberculosis Bacterium infects 1 in 3 people on the planet Drugs that cure TB were discovered in 1940s Results in death in 5 years in half of cases if untreated Kills 600,000 people ages 15-44 each year Estimated that TB will kill 35 M people in next 20 years

if situation does not change 2007:

9.27 M new cases (incidence) 500,000 cases of MDR-TB 1.7 M deaths 98% of deaths occur in developing world

http://www.who.int/tb

Global Tuberculosis Control 2009, WHO

Natural History of TB Infection

TB Pathophysiology

Active TB: Symptoms

Fever Night sweats Weight loss Weakness Coughs (productive with bloody sputum)

Airborne transmission Left untreated, one person with active

TB can cough millions of infectious droplets into the air

TB Pathophysiology TB and AIDS

People with AIDS are 10x more likely to develop active TB once infected

TB is the leading cause of death among HIV positive individuals, accounting for 13% of AIDS deaths worldwide

www.ourjeet.com/images/twinepidemics.gif

Diagnosis of Tuberculosis Skin test (PPD) Serum test Chest X-ray

Shows nodules in active TB

Sputum Acid-fast bacilli

Directly Observed Therapy (DOT)

A health care worker watches and helps as the patient swallows anti-TB medicines in his/her presence.

DOT shifts responsibility for cure from patient to health care system

Requires political commitment, accurate diagnosis, quality drugs, observation, follow up

DOT works well in many developing countries

6 month supply is $10 Cure rates of up to 95% even in

poorest countries 17 million patients worldwide have

been treated with DOT since 1995 25% of world’s population does not

have access to DOT.

Directly Observed Therapy (DOT)

Leading Causes of Mortality Ages 15-44

Developing World1. HIV/AIDS2. Unintentional injuries3. Cardiovascular diseases4. Tuberculosis

Developed World1. Unintentional injuries2. Cardiovascular diseases3. Cancer4. Self-inflicted injuries

3. Cancer

580,000 people ages 15-44 die as a result of cancer every year

Most common causes: Liver Cancer (68,000 deaths per year) Leukemias (65,000) Stomach Cancer (58,000) Breast Cancer (57,000)

Will be covered in depth in Lecture 4

4. Self-Inflicted Injuries

Burden of Self-Inflicted Injuries Risk Factors Associated with Suicide Methods of Suicide Screening and Prevention

Burden of Self-Inflicted Injuries

480,000 people ages 15-44 take their own lives each year (4th leading cause of death)

Unsuccessful attempts are 20x as frequent Unipolar depressive disorder ranks #1 for

DALYs in this age group in developed countries Second to HIV/AIDS in developing countries

Highest rate of completed suicides Men >65 years old

Highest rate of attempted suicides Men and women ages 20-24

Global suicide rates have increased 60% in the last 45 years

http://www.who.int/mental_health/prevention/suicide/suicideprevent/en/index.html

Risk Factors Associated with Suicide

Psychiatric illness Affective, substance abuse, personality, other

mental disorders Other risk factors

Social adjustment problems Serious medical illness Living alone Recent bereavement Personal history of suicide attempt or

completion Divorce or separation Unemployment

Methods of Suicide

Most common: Firearms are used in 60% of suicides

2nd leading cause: Men: Hanging Women: Drug overdose or poison

Alcohol is involved in 25-40% of suicides

Women attempt suicide more often; men are more often successful

Screening and Prevention

50-66% of all suicide victims visit physician <1 month before event

10-40% in the preceding week Hard to identify who is at risk

Direct questioning has low yield General questions about sleep

disturbance, depressed mood, guilt and hopelessness

Survey instruments aren’t good at predicting what will happen

Screening and Prevention

How do we quantify the efficacy of such questionnaires? Goal of screening:

Catch as many positives as possible, even at the risk of some false positives

Sensitivity: Se = probability of testing positive if you will commit

suicide

Sensitivity of best questionnaires: 56% (low)

suicidecommit who#

positive test who#Se

Screening and Prevention

How many false positives result? Positive predictive value:

PPV=probability of committing suicide if you test positive

PPV of best questionnaires: 3% (pathetic)

positive test who#

suicidecommit and positive test who#PPV

Screening and Prevention

SIGECAPS

Summary of Lecture 3

Developing World1. HIV/AIDS2. Unintentional injuries3. Cardiovascular diseases4. Tuberculosis

Developed World1. Unintentional injuries2. Cardiovascular diseases3. Cancer4. Self-inflicted injuries

Assignments Due Next Time

Project Task 1